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GI final - liver, pancreas, biliary tree
n/a
98
Accounting
Pre-School
12/19/2009

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Cards

Term
portal htn is defined as a portal pressure greater than?
Definition
10 mm Hg
Term
portal htn in cirrhosis arises from a blockade of which vessels?
Definition
intra-hepatic vessels (sinusoidal and post-sinusoidal d/t contraction of vascular smooth muscle cells and disruption of blood flow by scarring and formation of nodules)
Term
what in the liver is responsible for producing NO?
Definition
sinusoids
Term
portal htn is d/t 3 main components:
Definition
1. structural changes in the sinusoidal cells (capillarization - disappearance of fenestrae) 2. actual blocks within the liver, cirrhotic nodules (collagen deposition in the space of disse, fibrosis) 3. decrease in NO production by sinusoidal endothelial cells and increased sensitivity to vasoconstrictors
Term
3 features characterize cirrhosis systemically, they are:
Definition
1. hyperdynamic circulation 2. systemic vasodilation 3. sodium avidity
Term
systemic vasodilation in the cirrhotic state are sensed by what structures? what is their response to this vasodilation?
Definition
carotid and aortic baroreceptors and volume receptors in atrium --> stimulation of noradrenaline secretion
Term
desribe what happens to free water clearance in cirrhosis
Definition
altered, we retain more water when we're cirrhotic (although not in the arterial bed bc of vasodilation, therefore kidneys are not well perfused)
Term
what happens to plasma vol and cardiac output in patients with cirrhosis? peripheral resistance? what causes these effects
Definition
both increased and peripheral resistance decreased. caused by increased activity of plasma renin and aldosterone
Term
describe changing NO levels in the liver and systemically in cirrhosis
Definition
intrahepatic decrease in NO production by sinusoidal endothelial cells; systemically EXCESS NO production, which mediates the peripheral vasodilation
Term
what is the most important determining factor in the prognosis if cirrhosis?
Definition
ascites development (accumulation of lymph in abdominal cavity)
Term
ascites can be d/t a # of causes. what lab value will point to portal htn as the etiology of ascites?
Definition
serum plasma to ascites albumin gradient > 1.1 g/dL
Term
describe the 2 types of hepatorenal syndrome
Definition
HRS1 progressive impairment of renal function defined as doubling of baseline serum creatinine above 2.5 mg/dL in less than 2 weeks. HRS2 stable or slowly progressive impairment of renal function not meeting HRS1 criteria
Term
what are a few ways we treat ascites
Definition
bed rest with diet of Na restriction <2g/day; diuretics; paracentesis (give album or risk renal insufficiency!); transjugular intrahepatic portal-systemic shunt (risk mental status change); liver transplant
Term
how do we treat varices
Definition
beta blockers to decrease splanchnic circulation and portal htn; tx with banding of varices
Term
what are some things that cause infections in cirrhotic patients
Definition
impaired reticuloendothelial system (d/t splenomegaly); portosystemic shunting (get toxic stuff in systemic circulation --> hypergammaglobulinemia); increased intestinal permeability; contamination of ascites fluid (seeding from LN)
Term
what is probably responsible for the increase in circulating ammonia associated with encephalopathy in cirrhosis
Definition
portosystemic shunting --> bacteria create ammonia in gut --> systemic circulation --> brain
Term
how does gabaergic neurotransmission mediate encephalopathy in cirrhotic patients
Definition
increased availability of endogenous benzodiazepines --> conformation change of gaba receptor --> cl- comes into the cell --> inhibitory neurotransmission
Term
injury of which cell in the liver stimulates the fibrotic process?
Definition
ito cells (stellate cells) --> injury induces them to become facultative fibroblastic cells --> deposit collagen in the liver (space of disse - normally has thin strands of type IV collagen while rest of liver has type I and III. in pathology, collagen types I and III are deposited in space of disse) --> cirrhosis
Term
the preservation of _______ in the liver permits complete regeneration (reversible injury) following insult, whereas their destruction leads to scarring, fibrosis, and irreversible cirrhosis.
Definition
reticulin (stacks of collagin in space of disse produced by ito cells)
Term
fulminant liver failure is what?
Definition
when encephalopathy develops within 2 weeks of onset of jaundice
Term
what are the main causes of fulminant liver failure?
Definition
acetomenaphen OD (50%); autoimmune (15%); exposure to toxins (15%); HBV (8%); HAV (4%)
Term
main causes of hepatorenal syndrome?
Definition
sodium retention, impaired free-water excretion, decreased renal perfusion, decreased glomerular filtration rate
Term
hepatopulmonary syndrome diagnosed by classic triad
Definition
chronic liver disease, hypoxemia, intrapulmonary vascular dilations
Term
what is the key mediator in hepatopulmonary syndrome?
Definition
enhanced production of NO by the lung (causes rapid blood flow thru pulmonary vessels --> lack of uniform blood flow, ventilation perfusion mismatch, limitation of oxygen diffusion...)
Term
nodularity in the liver is a result of what pathologic process?
Definition
cycles of hepatocyte regeneration and scarring, confined by fibrous septa
Term
what causes the arterial vasodilation (increase in NO) in cirrhosis?
Definition
portosystemic shunt --> blood bypasses the kupffer cells --> decreased function of kupffer cells (macrophage/phagocytosing function) --> reduced clearance of bacterial DNA absorbed from the gut --> NO production stimulated
Term
what creates "feathery degeneration"
Definition
cholestasis --> accumulation of droplets of bile pigment in the hepatocytes --> fine foamy appearance of hepatocytes
Term
diffuse parenchymal damage (pan-acinar) is characteristic of which 3 types of liver damage?
Definition
fulminant hepatic injury, fulminant acute viral hepatitis, severe hepatotoxic drug reaction
Term
periportal damage denotes what kind of liver pathology?
Definition
piecemeal necrosis --> chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis
Term
pericentral damage is indicative of what liver pathology?
Definition
chemical toxicity, ischemia
Term
what are the four characteristic histological findings associated with alcoholic hepatitis?
Definition
1. hepatocyte swelling and necrosis; 2. mallory bodies (cytokeratin 8 and 18) 3. neutrophilic rxn (accumulate in area of degeneration) 4. fibrosis (almost always activation of ito cells --> fibrosis)
Term
3 causes of fatty liver change
Definition
1. excess NADH from alcohol metabolism 2. impaired assembly and secretion of lipoproteins 3. increased peripheral catabolism of fat
Term
3 primary pathways of alcohol degradation
Definition
1. cytosolic alcohol dehydrogenase (>80%) 2. microsomal ethanol oxidizing system 3. catalase
Term
alcohol dehydrogenase acts in what part of the liver?
Definition
hepatocellular cytosol (activity genetically determined)
Term
what is the primary enzyme of the microsomal ethanol oxidizing system? where does it work?
Definition
cytochrome P4502E1; inducible by several drugs and alcohol consumption; works in microsome (ER)
Term
where does catalase work?
Definition
peroxisome, mitochondria, role is minimal
Term
what are the consequences of having high NADH
Definition
increased a-glycerophosphate levels --> increased FA synthesis and hepatocellular accumulation of trigs; decreased mitochondrial oxidation of FA --> further intrahepatocyte accumulation of FA
Term
what is the consequence of having high acetylaldehyde?
Definition
microtubular alterations --> disrupt protein secretion and water/electrolyte transport --> ballooning degeneration (hepatomegaly and cellular necrosis); also binds glutathione and depletes concentration of free radical scavengers --> increases lipid peroxidation and decreases ability to scavenge drug metabolites
Term
what are the clinical findings of fatty liver?
Definition
hepatomegaly, normal LFTs, minimal ALP increase, centrilobular steatosis on bx
Term
what are the clinical manifestations of alcoholic hepatitis?
Definition
anorexia, weight loss, fever, fatigue, RUQ pain, nausea; hepatomegaly, jaundice, ascites, peripheral edema, encephalopathy; increased LFTS (<300 IU/L usually), elevated ALP; bx: hepatocellular necrosis, pmn infiltration, pericentral fibrosis, mallory bodies
Term
what are the 3 ways drugs/toxins can induce liver injury?
Definition
1. direct toxicity of hepatocytes of biliary epithelial cells --> necrosis, apoptosis, disruption of cellular function (production of free radicals) 2. hepatic conversion of xenobiotic to an active toxin (electrophilic metabolite of offending drug produced by p450 system, escapes detoxification and covalently binds to cellular constituents disturbing their function) 3. immune mechanisms (drug or metabolite acting as a hapten to convert cellular protein to immunogen; prototype is halothane)
Term
describe how halothane leads to liver injury
Definition
prototypic immunologic mediated injury; metabolite (trifluoroacetyl) reacts with hepatocellular proteins --> patient develops serum antibodies to these neoantigens
Term
budd-chiari syndrome associated with?
Definition
oral contraceptives
Term
describe reye syndrome
Definition
rare and potentially fatal syndrome of mitochondrial dysfunction (pleomorphic enlargement, disruption of ultrastructure, distortion of cristae, formation of electron-lucent matrices) in liver, brain, elsewhere; children; extensive accumulation of fat droplets (microvesicular steatosis); assoc with aspiriin use for relief of fever; progressive hepatic failure and encephalopathy
Term
what is eclampsia?
Definition
hemorrhage and circulatory collapse --> DIC --> necrosis of hepatic parenchyma; characterized by maternal HTN, proteinuria, peripheral edema, coag abn; hyper-reflexia and convulsions
Term
who is susceptible to acute fatty liver of pregnancy? and what causes it?
Definition
women in 3rd trimester of pregnancy; when both mother and father carry heterozygous deficiency in mitochondrial long-chain 3-hydroxyacyl coenzyme A dehydrogenase. homozygous deficient fetus --> 3-hydroxylacyl metabolites produced by fetus or placenta washed away into maternal circ --> hepatic toxicity
Term
what are the clinical findings of acute fatty liver of pregnancy?
Definition
microvesicular steatosis on bx; bleeding, nausea, vomiting, jaundice, coma; most commonly runs a mild course but can progress within days to hepatic failure and death
Term
what is the primary tx for acute fatty liver of pregnancy?
Definition
pregnancy termination
Term
what causes intrahepatic cholestatis of pregnancy?
Definition
altered hormonal state of pregnancy + biliary defects --> pure benign cholestasis (steroid-induced hepatocellular damage).
Term
what are the clinical findings of intrahepatic cholestasis of pregnancy?
Definition
pruritis in 3rd trimester (can be really bad); darkening of urine, light stools, jaundice; puts mother at risk for gallstones and malabsorption; increased incidence of fetal distress, still births and premature birth
Term
tx for intrahepatic cholestasis of pregnancy?
Definition
pregnancy termination
Term
what is the common cause of liver abscesses in developing countries?
Definition
parasitic infections, protozoa, helminths
Term
what is the common cause of liver abscesses in non-developing countries?
Definition
bacterial origin, complication of infection elsewhere
Term
describe the pathogenesis of autoimmune hepatitis and what it's genetically associated with
Definition
T-cell mediated autoimmunity in which hepatocyte injury is caused by IFN-gamma produced by CD4 and CD8 cells and by CD8 T-cell mediated cytotoxicity; genetic factors play a role (HLA-B1, B8, DR3, and DR4, DRB1) are common and also common are associations with other autoimmune disorders (sjogrens, lupus, RA, UC)
Term
Type I autoimmune hepatitis associated with what pattern of circulating autoantibodies? and which HLA haplotypes
Definition
(young women) anti-nuclear antibodies, anti-actin antibodies, anti-smooth muscle antibodies, pANCA, and HLA-DR3, DR4
Term
autoimmune hepatitis Type II associated with what pattern of autoantibodies? and which HLA haplotypes
Definition
(children, mediterranean) anti-liver kidney microsome-1 (ALKM-1) antibodies, anti-liver cytosol-1 (ACL-1), HLA-DRB1, HLA-DQB1
Term
what is histologically characteristic of autoimmune hepatitis?
Definition
clusters of plasma cells in the interface of portal tracts and hepatic lobules
Term
low-flow states (as with shock or left ventricular failure) results in ischemia of which zone of hepatic acinus?
Definition
zone 3
Term
what are 2 things that might cause sinusoidal occlusion and therefore hepatic infarction?
Definition
sickle cell, DIC
Term
acute impairment of vascular outflow in the liver will result in what kind of damage to the liver?
Definition
centrilobular congestion, hemorrhagic necrosis
Term
chronic impairment of vascular outflow in the liver will result in what sort of damage?
Definition
atrophy of centrilobular hepatocytes, pericentral fibrosis
Term
what causes the characteristic nutmeg liver?
Definition
combination of right sided heart failure --> passive liver congestion; + left sided heart failure --> hepatic hypoperfusion and necrosis in zone3 (centrilobular necrosis); together = centrilobular hemmorhagic necrosis --> variegated, mottled red apperance = NUTMEG LIvER!
Term
what is budd-chiari syndrome?
Definition
obstruction of two or more major hepatic veins --> liver enlargement, pain, ascites (massive passive congestion), dilation of central veins and sinusoids, fibrosis
Term
what are some of the more common causes behind hepatic veno-occlusive disease?
Definition
hepatotoxic alkaloids found in jamaican bush tea; post-allogenic-bone-marrow-transplant; anti-neoplastics, immunosuppressants, hepatic irradiation.
Term
describe the pathogenesis of veno-occlusive disease
Definition
toxic injury to sinusoidal endothelium --> endothelial lining cells round up and slough off the sinusoidal wall --> embolize downstream and obstruct sinusoidal blood flow --> accumulation of cellular debris in central vein; also, proliferation of ito cells and subendothelial fibroblasts in central vein --> fibrosis and deposition of ECM in the sinusoids -->obliteration of the small veins of the liver (thrombosis may propagate to larger hepatic veins mimicking budd-chiari)
Term
annular pancreas is associated with what other condition?
Definition
trisomy21
Term
what is a macroamylase and what lab findings will pick it up?
Definition
heterogenous complex of normal amylase + IgA, IgG or polysaccharide. persistant increase in serum amylase with normal or low urine amylase
Term
what is the etiology of cystic fibrosis?
Definition
autosomal recessive disorder of ion transport. mutation of transmembrane conductance regulator (CFTR) gene on chromosome 7 --> encodes epithelial chloride channel protein --> defective chloride transport --> abnormally dehydrated tenacious secretions of all exocrine glands. heterozygotes no clinical sx.
Term
what are the clinical signs of cystic fibrosis
Definition
recurrent pulm inf, pancreatic insufficiency (thick secretions plug ducts, cause chronic inflammation with atrophy of acini, fibrosis, dilatation, cystic duct changes --> pancreatic lipase deficiency --> malapsorption of fat & nutrients --> steatorrhea & malnutrition) men infertile d/t duct obstruction (azospermia), sweat chloride level elevated (>60mmol/L diagnostic)
Term
how do we dx hemochromatosis?
Definition
transferrin saturation >60% in men and >50% in women --> confirm with fasting transferrin saturation and ferritin levels --> liver bx with assay for iron to confirm and assess extent
Term
what effect does hemochromatosis have on the pancreas? other organs? (pathophysiology)
Definition
iron deposits in acinar cells, duct cells, B cells of the islets --> pancreas slightly enlarged, deep brown d/t accumulated hemosiderin --> progressive fibrosis with atrophy --> "bronze" diabetes d/t similar pigmentation in skin (hemosiderin + increase in melanin prod). hypogonadism (atrophy, infertility), pituitary dysfunc, cardiomegaly, psuedo-gout, cirrhosis, hcc)
Term
what are the 3 main features characterizing hemochromatosis?
Definition
micronodular cirrhosis, diabetes mellitus, skin pigmentation
Term
hereditary hemochromatosis etiology
Definition
HLA-linked, autosomal recessive, d/t mutation in HFE (located on short arm of chromosome 6) --> lack of hepcidin expression --> iron overload
Term
what is the name for pancreatic changes associated with protein-calorie malnutrition?
Definition
kwashiorkor
Term
what are the causes of idiopathic acute pancreatitis?
Definition
(10-20%) germline mutations of PRSS1 (cationic trypsinogen gene) --> alteration of a site that is essential for the inactivation of trypsin by trypsin itself --> trypsin becomes resistant to cleavage by other trypsin molecules --> trypsin activated in pancreas --> can activate other digestive enzymes --> pancreatitis!; germline mutation of SPINK1 (pancreatic secretory trypsin inhibitor) --> pancreas not protected against autodigestion by activated trypsin --> pancreatitis
Term
what accounts for 80% of the cases of acute pancreatitis in western world?
Definition
alcoholism and biliary tract disease (gallstones also frequently found)
Term
what are the 2 subtypes of acute pancreatitis that we can histologically identify?
Definition
1. incidental/edematous pancreatitis (mild) 75-80% - peripancreatic fat necrosis (from enzymatic activity of lipase) and interstitial edema, no mortality, spontaneous recovery. 2. hemorrhagic pancreatitis (severe) necrosis of pancreas with hemorrhage may cause shock and death, necrosis starts coagulative then liquefactive
Term
what is the basic pathophysiology behind acute pancreatitis?
Definition
premature activation of inactive proenzyme trypsinogen to trypsin --> activates most of theo ther digestive enzymes --> tissue damage and necrosis of pancreas, surrounding fat and adjacent struc
Term
what are 3 possible complications of acute pancreatitis?
Definition
hypocalacemia, mild jaundice, sepsis-like syndrome d/t digestive enzymes in the systemic circ --> systemic immune response syndrome w/severe systemic complications (75% of patients with acute pancreatitis recover)
Term
what lab tests do we do to check for acute pancreatitis?
Definition
serum amylase (rises 2-12 hrs after onset, peak 20-30 hrs, wnl in 3-5 days); urinary amylase (rises 6-10 hrs after onset, persists for 4 days); amylase can be nonspecific, so do serum lipase to confirm pancreatic etiology (increases in 4-8 hrs, elevated for 8-14 days); hyperglycemia, elevated bilirubin, leukocytosis; negative serum trypsinogen-2 level excludes acute pancreatitis
Term
what is the cause of idiopathic chronic pancreatitis?
Definition
d/t cystic fibrosis, caused by mutation of CFTR gene --> protein plugging of ducts --> other features of cystic fibrosis absent
Term
describe mucinous cystadenomas
Definition
women, multiloculated, lined by mucin-producing columnar epithelium, may be malignant
Term
describe serous cystadenomas
Definition
7th decade of life, benign, produce a palpable mass, variably sized cysts lined by cuboidal epithelial cells with clear, glycogen-rich cytoplasm
Term
what are some risk factors for pancreatic carcinoma?
Definition
old age, male predominance, blacks, native americans, cig smokers, chronic pancreatitis, diabetes mellitus, alcohol, coffee
Term
what is courvoisier sign?
Definition
acute painless dilatation of the gallbladder d/t common bile duct obstruction by tumor (1/3 of pancreatic carcinoma pts)
Term
what is trousseau sign?
Definition
migratory thrombophlebitis, paraneoplastic feature of pancreatic carcinoma (10%) --> d/t platelet aggregating factors and procoagulants from the tumor
Term
describe intraductal papillary mucinous neoplasm
Definition
arise in main duct or major branches, produce benign and malig cysts that contain mucin, classified according to degree of epithelial atypia
Term
what is a klatskin tumor
Definition
pancreatic carcinoma that arises in the common bile duct --> localized resection can remove it
Term
what is the most frequently altered oncogene in pancreatic cancer?
Definition
KRAS
Term
what is the most frequently inactivated tumor suppressor gene in pancreatic cancer? (next?)
Definition
p16. then SMAD4, p53
Term
what are KRAS, CEA and CA19-9 useful for in pancreatic cancer?
Definition
if theyre elevated upon diagnosis, can be used to monitor recurrence
Term
why are some gastrinoma patients hypercalcemic?
Definition
parathyroid-hormone production or bc patients with MEN1 (1/3 of the time assoc with ZES) may develop hyperparathyroidism
Term
what % of ZES patients have malignant tumors? what % have metastases?:
Definition
70-90% malignant at diagnosis; 50% metatstatic, mostly to liver
Term
describe glucagonomas
Definition
rare, origin is alpha cells of pancreas --> secrete glucagon --> glycogenolysis (breakdown of glycogen) and gluconeogenesis (generation of glucose) --> raise blood glucose levels --> mild diabetes, necrotizing migratory erythematous rash, anemia, venous thromboses, severe infections; 40-70 yrs, female predominance, 2/3 malignant, large tumors, locally invasive
Term
describe somatostatinoma
Definition
delta cells; rare, solitary; inhibits pituitary release of growth hormone and inhibits secretion by alpha, beta, D cells, regulates glucose homeostasis.--> mild diabetes, gallstones, steatorrhea, hypochlorhydria (d/t inhibitory effect of somatostatin on other islet and neuroendocrine cells) may also secrete ACTH and calcitonin; most malig with mets at dx
Term
describe VIPoma
Definition
rare; induces glycogenolysis and hyperglycemia --> explosive and profuse watery diarrhea with hypokalemia and hypochlorhydria. large, solitary, malig
Term
describe PPoma
Definition
in islets in head of pancreas --> stimulates gastric mucosal enzyme secretion that inhibits production of gastric acid and exocrine pancreas secretions and exocrine pancreas secretions; tumors single; benign; no clinical syndrome
Term
describe carcinoids
Definition
synthesize seratonin and motilin. rare, malig. atypical carcinoid syndrome: facial flush, hypotension, periorbital edema, lacrimation; (liver mets = classical carcinoid syndrome)
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